ACTIONS OF MU-OPIOID, DELTA-OPIOD AND KAPPA-OPIOID AGONISTS AND ANTAGONISTS ON MOUSE PRIMARY AFFERENT NEURONS IN CULTURE

  • 1 October 1987
    • journal article
    • research article
    • Vol. 243  (1) , 258-263
Abstract
The effects of selective mu, delta and kappa opioid agonists and antagonists were studied on somatic calcium-dependent action potentials recorded from mouse dorsal root ganglion (DRG) neurons grown in dissociated cell culture. The mu selective agonist, PL 017, and the delta selective agonist, [D-Pen2,L-Pen5] enkephalin (DPLPE), reduced action potential duration of a subpopulation (21/56) of DRG neurons. Leucine-enkephalin reduced action potential duration of all neurons sensitive to PL 017 or DPLPE, whereas 85% of neurons responding to leucine-enkephalin responded to either PL 017 or DPLPE. Only 15% of neurons responded to both PL 017 and DPLPE. There was no significant difference in the repsonse to PL 017 or DPLPE when compared to leucine-enkephalin. In another experiment, the kappa selective agonist dynorphin A (DYN A), PL 017 and DPLPE reduced action potential duration of a subpopulation (15/67) of DRG neurons. There was a heterogeneous response among neurons to PL 017, DPLPE and DYN A inasmuch as 21.4% of neurons responded to all three agonists, 35.7% responded to PL 017 and DYN A, 35.7% responded only to PL 017 and 7.1% responded only to DYN A. Responses to the mu selective agonist PL 017 were antagonized by the reversible opioid antagonist naloxone and the selective mu antagonist SMS 201-995 in a concentration-dependent fashion. Responses to PL 017 were not altered by the selectve delta antagonist ICI 174864. Responses to PL 017 were reduced by the irreversible, selective mu antagonists .beta.-fulnaltrexamine and naloxonazine in a concentration-dependent fashion. These results demonstrate that mu, delta and kappa opioid receptors that are coupled to calcium or potassium ion channels can be characterized on DRG neurons in cell culture by the use of selective opioid agonists and antagonists and confirm a heterogeneous distribution among nerons for all three receptor types.